Neuron Reprogramming and Status of p53 in Head and Neck Cancer
Posted: Monday, March 16, 2020
In the journal Nature, Moran Amit, MD, PhD, of The University of Texas MD Anderson Cancer Center, and colleagues suggest that the absence of the tumor-suppressing gene p53 may play a key role in the buildup of neurons in the tumors of patients with head and neck cancer. The authors suggest that using treatments including blood pressure and irregular heartbeat medications may ultimately improve outcomes in this patient population.
“Tons of studies show that patients who have lots of nerves in their tumor are doing worse— recurrence rates are higher, survival is shorter,” said Dr. Amit, in an MD Anderson press release. “We really haven’t understood whether the tumor was growing into the nerves or the nerve growing into the tumor and what signaling drove those interactions,” added co-senior author Jeffrey N.Myers, MD, PhD.
A high concentration of neurons was found in p53-deficient mouse models and human xenograft tumors of oral cavity squamous cell carcinoma. Additionally, there was increased neural growth in closets of nerves that had p53-deficient oral cavity squamous cell carcinoma. The investigators found that miRNAs in vesicles from p53-deficient tumors made contact with existing sensor nerves and transformed them into the adrenergic type. These neoadrenergic nerves were the ones entering the tumor, according to the authors. Using these results, the researchers examined the nerves in the tumors of 70 patients who received treatment at MD Anderson. Tumors with adrenergic nerve density were linked with lower recurrence-free and overall survival.
Based on the research findings, the authors believe the neurons reprogram and become an adrenergic phenotype, which leads to tumor growth. The investigators are developing clinical trials of adrenergic blockers that could be used in combination with other drugs in the treatment of patients with head and neck cancer.
Disclosure: The study authors reported no conflicts of interest.